Increased rate of disappearance of serum probenecid in barbital dependent rats.

Rats were made barbital dependent by administration of barbital in their drinking water. Subsequently, the rats were either not withdrawn (BN) or withdrawn from barbital for 24 h (BW-24). Before sacrifice, probenecid was administered to measure brain serotonin turnover. A statistically significant decrease in 5-hydroxyindoleacetic acid (5-HIAA) accumulation was observed in the cerebral cortex medulla pons and midbrain. Subsequentialy, serum levels of probenecid were also measured by gas chromatography to determine if chronic barbital consumption might affect circulating probenecid. By ninety minutes following probenecid administration, serum probenecid levels in BN and BW-24 rats were significantly lower than control while a probenecid metabolite was significantly increased. The significantly reduced accumulation of 5-HIAA in brain areas of BN and BW-24 rats is probably the result of the more rapid decline of probenecid rather than a true decrease in serotonin turnover.